Isis Pharmaceuticals, Inc.

Other

Baylor College of Medicine

Lex M Cowsert

Brett P Monia

C Frank Bennett

Jacqueline R Wyatt

Brenda F Baker

Elizabeth J Ackermann

Susan M Freier

David J Ecker

Robert McKay

Stanley T Crooke

Christopher K Mirabelli

Donna T Ward

Madeline M Butler

Eric E Swayze

Kenneth W Dobie

Muthiah Manoharan

Hong Zhang

Sanjay Bhanot

Nicholas M Dean

William A Gaarde

Thomas P Condon

Ian Popoff

Alexander H Borchers

Jennifer K Taylor

Mark J Graham

Bert W O'Malley

John McNeil

Andrew M Siwkowski

Timothy A Vickers

Kevin P Anderson

Vickie L Brown-Driver

Michael J Weber

Joshua N Finger

Susan F Murray

Pamela S Nero

Loren J Miraglia

Henri M Sasmor

Kathleen Myers

M Luisa Roberts

Cara Ohashi

Patrick Allen Marcotte

Xaoxing S Xu

Richard A Roth

Madelline M Butler

Paul R Clark

Douglas G Brooks

Disclosed herein are antisense compounds and methods for decreasing CD40. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to CD40 include hyperproliferative disorders, graft versus host disease (GVHD), graft rejection, asthma, airway hyperresponsiveness, chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and certain forms of arthritis.

Modulation of CD40 expression

Compounds, compositions and methods are provided for modulating the expression of PTP1B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTP1B. Methods of using these compounds for modulation of PTP1B expression and for treatment of diseases associated with expression of PTP1B are provided.

Antisense modulation of PTP1B expression

Antisense compounds, compositions and methods are provided for modulating the expression of CD40. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD40. Methods of using these compounds for modulation of CD40 expression and for treatment of diseases associated with CD40 are provided.

Antisense modulation of CD40 expression

Compounds, compositions and methods are provided for modulating the expression of RANKL. The compositions comprise oligonucleotides, targeted to nucleic acid encoding RANKL. Methods of using these compounds for modulation of RANKL expression and for diagnosis and treatment of disease associated with expression of RANKL are provided.

Modulation of RANKL expression

Interative, preferably computer based iterative processes for generating synthetic compounds with desired physical, chemical and/or bioactive properties, i.e., active compounds, are provided. During iterations of the processes, a target nucleic acid sequence is provided or selected, and a library of candidate nucleobase sequences is generated in silico according to defined criteria. A 'virtual' oligonucleotide chemistry is chosen and a library of virtual oligonucleotide compounds having the selected nucleobase sequences is generated. These virtual compounds are reviewed and compounds predicted to have particular properties are selected. The selected compounds are robotically synthesized and are preferably robotically assayed for a desired physical, chemical or biological activity. Active compounds are thus generated and, at the same time, preferred sequences and regions of the target nucleic acid that are amenable to oligonucleotide or sequence-based modulation are identified.

System of components for preparing oligonucleotides

Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Antisense modulation of survivin expression

Compositions and methods are provided for the modulation of ras expression. Oligonucleotides are provided which are targeted to nucleic acids encoding human ras. Oligonucleotides specifically hybridizable with mRNA encoding human H-ras, Ki-ras and N-ras are provided. Such oligonucleotides can be used for therapeutics and diagnostics as well as for research purposes. Methods are also disclosed for modulating ras gene expression in cells and tissues using the oligonucleotides provided, and for specific modulation of expression of activated ras. Methods for diagnosis, detection and treatment of conditions, or particular cancers, associated with ras are also disclosed.

Antisense oligonucleotide inhibition of ras

Antisense compounds, compositions and methods are provided for modulating the expression of PTPN12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTPN12. Methods of using these compounds for modulation of PTPN12 expression and for treatment of diseases associated with expression of PTPN12 are provided.

Antisense modulation of PTPN12 expression

Antisense compounds, compositions and methods are provided for modulating the expression of NF-kappa-B p65 subunit. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding NF-kappa-B p65 subunit. Methods of using these compounds for modulation of NF-kappa-B p65 subunit expression and for treatment of diseases associated with expression of NF-kappa-B p65 subunit are provided.

Antisense modulation of NF-kappa-B p65 subunit expression

Antisense compounds, compositions and methods are provided for modulating the expression of Her-2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Her-2. Methods of using these compounds for modulation of Her-2 expression and for treatment of diseases associated with expression of Her-2 are provided.

Antisense inhibition of Her-2 expression

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Carlsbad, CA, United States of America

Lex M Cowsert